NEIL3 contributes to the Fanconi anemia/BRCA pathway by promoting the downstream double-strand break repair step

Niu Li, Yufei Xu, Hongzhu Chen, Lina Chen, Yi Zhang, Tingting Yu, Ruen Yao, Jing Chen, Qihua Fu, Jia Zhou, Jian Wang
2022 Cell Reports  
Interstrand crosslinks (ICLs) repair by the canonical Fanconi anemia (FA) pathway generates double-strand breaks (DSBs), which are subsequently repaired by the homologous recombination (HR) pathway. Recent studies show that the NEIL3 DNA glycosylase repairs psoralen-ICLs by direct unhooking. However, whether and how NEIL3 regulates MMC and cisplatin-ICL repair remains unclear. Here we show that NEIL3 participates in DSB repair step of ICL repair by promoting HR pathway. Mechanistically, NEIL3
more » ... recruited to the DSB sites through its GRF zinc finger motifs. NEIL3 interacts with the DSB resection machinery, including CtIP, the MRE11-RAD50-NBS1 (MRN) complex, and DNA2, which is mediated by the GRF zinc finger motifs. In addition, NEIL3 is necessary for the chromatin recruitment of the resection machinery, and depletion of NEIL3 decreases end resection and compromises HR. Taken together, our results show that NEIL3 plays an important role in MMC/cisplatin-ICL repair by promoting the HR step in FA/BRCA pathway.
doi:10.1016/j.celrep.2022.111600 pmid:36351389 fatcat:3oydcxyy5rf7xeb4oynbdgypxe